Skip to main content
SpringerLink
Log in

HIV-1 with Predicted CXCR4 Genotype Identified in Clade C from India

  • Short Communication
  • Published:
Molecular Diagnosis & Therapy Aims and scope Submit manuscript

Abstract

Background and objective: HIV-1 uses co-receptors CCR5 and CXCR4 in addition to CD4 for viral entry into cells. CCR5 is used in the early stages of HIV-1 infection, but viruses that utilize CXCR4 for viral entry emerge in the later stages. This is not common among clade C strains, with previous data from India showing the absence of the emergence of CXCR4-using strains. Sequence analysis has demonstrated that the V3 loop plays a very important role in determining the syncytium-inducing (SI) phenotype. The V3 region of the SI variants were observed to have positively charged amino acids at positions 11 and/or 25 and also a overall higher charge. This study looked at co-receptor usage among HIV-1 strains in India from individuals who were antiretroviral therapy (ART) naïve and those not responding to ART.

Methods: Amplification and sequencing of the HIV-1 env gp120 V3 region was done on 40 ART-naïve individuals, who were selected for the study based on their CD4 counts, and eight patients who had not responded to ART. The sequences were submitted to Geno2Pheno and Web PSSM. The pol gene sequences of these strains were submitted to the REGA HIV-1 subtyping tool.

Results: Forty-seven strains were identified as clade C and one strain as clade A1. Geno2Pheno identified three CXCR4-using strains, and the Web PSSM clade C matrix identified two.

Conclusion: We report, for the first time, CXCR4-using strains among HIV-1 clade C strains circulating in India.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I
Fig. 1
Fig. 2

References

  1. Berger EA, Murphy PM, Farber JM. Chemokine receptors as HIV-1 coreceptors: roles in viral entry, tropism, and disease. Annu Rev Immunol 1999; 17: 657–700

    Article  PubMed  CAS  Google Scholar 

  2. Koot M, Keet IP, Vos AH, et al. Prognostic value of HIV-1 syncytium-inducing phenotype for rate of CD4+ cell depletion and progression to AIDS. Ann Intern Med 1993; 118: 681–8

    PubMed  CAS  Google Scholar 

  3. Koot M, Vos AH, Keet RP, et al. HIV-1 biological phenotype in long-term infected individuals evaluated with an MT-2 cocultivation assay. AIDS 1992; 6: 49–54

    Article  PubMed  CAS  Google Scholar 

  4. Ping LH, Nelson JA, Hoffman IF, et al. Characterization of V3 sequence heterogeneity in subtype C human immunodeficiency virus type 1 isolates from Malawi: underrepresentation of X4 variants. J Virol 1999; 73: 6271–81

    PubMed  CAS  Google Scholar 

  5. Cecilia D, Kulkarni SS, Tripathy SP, et al. Absence of coreceptor switch with disease progression in human immunodeficiency virus infections in India. Virology 2000; 271: 253–8

    Article  PubMed  CAS  Google Scholar 

  6. Connell BJ, Michler K, Capovilla A, et al. Emergence of X4 usage among HIV-1 subtype C: evidence for an evolving epidemic in South Africa. AIDS 2008; 22: 896–9

    Article  PubMed  Google Scholar 

  7. Mueller MC, Bogner JR. Treatment with CCR5 antagonists: which patient may have a benefit? Eur J Med Res 2007; 12: 441–52

    PubMed  CAS  Google Scholar 

  8. Freed EO, Martin MA. HIVs and their replication. In: eiKnipe DM, Howley PM, editors. Fields virology. 4th ed. Philadelphia: Lippincott Williams & Wilkins 2001; 1971–2042

    Google Scholar 

  9. Jensen MA, van’t Wout AB. Predicting HIV-1 coreceptor usage with sequence analysis. AIDS Rev 2003; 5: 104–12

    PubMed  Google Scholar 

  10. Kandathil AJ, Kannangai R, David S, et al. CD4+ and CD8+ T cell estimation by a micro-capillary cytometry technology compared with flow cytometry. Clin Diagn Lab Immunol 2005; 12: 1006–9

    PubMed  CAS  Google Scholar 

  11. Kannangai R, Kandathil AJ, Ebenezer DL, et al. Evidence for lower CD4+ T cell and higher viral load in asymptomatic HIV-1 infected individuals of India (south): implications for therapy initiation. Indian J Med Microbiol 2008; 26: 217–21

    Article  PubMed  CAS  Google Scholar 

  12. Mullins JI. Heteroduplex mobility analysis manual [online]. Available from URL: http://ubik.microbiol.washington.edu/HMA/html/primers.html [Accessed 2007 Dec 12]

  13. 13. Nomenclature for incompletely specified bases in nucleic acid sequences: recommendations 1984. Nomenclature Committee of the International Union of Biochemistry (NC-IUB). Proc Natl Acad Sci U S A 1986; 83: 4–8

    Article  Google Scholar 

  14. European Bioinformatics Institute. ClustalW [computer program; online]. Available from URL: http://www.ebi.ac.uk/Tools/clustalw [Accessed 2008 Jun 2]

  15. Geno2pheno (coreceptor) [computer program; online]. Available from URL: [http://co-receptor.bioinf.mpi-inf.mpg.de/index.php] [Accessed 2008 Apr 23]

  16. Web PSSM [computer program; online]. Available from URL: http://ubik.microbiol.washington.edu/computing/pssm/ [Accessed 2008 Sep 19]

  17. WebLogo [computer program; online]. Available from URL: http://weblogo.berkeley.edu/logo.cgi [Accessed 2009 Jan 5]

  18. Crooks GE, Chandonia JM, Brenner SE. WebLogo: a sequence logo generator. Genome Research 2004; 14: 1188–90

    Article  PubMed  CAS  Google Scholar 

  19. Kandathil AJ, Kannangai R, Abraham OC, et al. The frequency of HIV-I drug resistance mutations among treatment naïve individuals at a tertiary care centre in south India. Int J STD & AIDS. In press

  20. Stanford University HIV drug resistance database. REGA HIV-1 subtyping tool — version 2.0 [computer program; online]. Available from URL: http://dbpartners.stanford.edu/RegaSubtyping/ [Accessed 2008 Jun 21]

  21. Tamura K, Dudley J, Nei M, et al. MEGA4: molecular evolutionary genetics analysis (MEGA) software version 4.0. Mol Biol Evol 2007; 24: 1596–9

    Article  PubMed  CAS  Google Scholar 

  22. Center for Evolutionary Functional Genomics. MEGA4 [computer program; online]. Available from URL: http://megasoftware.net/index.html [Accessed 2008 Jun 23]

  23. Jensen MA, Coetzer M, van’t Wout AB, et al. A reliable phenotype predictor for human immunodeficiency virus type 1 subtype C based on envelope V3 sequences. J Virol 2006; 80: 4698–704

    Article  PubMed  CAS  Google Scholar 

  24. Garrido C, Roulet V, Chuecaau N, et al. Evaluation of eight different bioinformatics tools to predict viral tropism in different human immunodeficiency virus type 1 subtypes. J Clin Microbiol 2008; 46: 887–91

    Article  PubMed  Google Scholar 

  25. Westby M, Lewis M, Whitcomb J, et al. Emergence of CXCR4-using human immunodeficiency virus type 1 (HIV-1) variants in a minority of HIV-1-infected patients following treatment with the CCR5 antagonist maraviroc is from a pretreatment CXCR4-using virus reservoir. J Virol 2006; 80: 4909–20

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

Mark Jensen now works at Fortinbras Research, Buford, GA, USA.

This work was supported by intramural funding. The authors have no conflicts of interest that are directly relevant to the content of this study.

Author information

Authors and Affiliations

  1. Department of Clinical Virology, Christian Medical College, Vellore, 632004, India

    Abraham Joseph Kandathil,  Rajesh Kannangai & Gopalan Sridharan

  2. Department of Internal Medicine, Christian Medical College, Vellore, India

    Oriapadickal Cherian Abraham

  3. Department of Dermatology, Christian Medical College, Vellore, India

    Susanne Alexander Pulimood

  4. Department of Genetics and Epidemiology, University of Georgia Athens, Atlanta, Georgia, USA

    Mark A. Jensen

Authors
  1. Abraham Joseph Kandathil
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rajesh Kannangai
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Oriapadickal Cherian Abraham
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Susanne Alexander Pulimood
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mark A. Jensen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Gopalan Sridharan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rajesh Kannangai.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Joseph Kandathil, A., Kannangai, R., Cherian Abraham, O. et al. HIV-1 with Predicted CXCR4 Genotype Identified in Clade C from India. Mol Diag Ther 13, 19–24 (2009). https://doi.org/10.1007/BF03256311

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03256311

Keywords

Search

Navigation